Gold-Catalyzed [2+2] Cyclization of Alkyne-propargylic Pivaloates to Fused Bicyclic Compounds

Abstract

We discovered a new and highly convenient gold-catalyzed cyclization of alkyne-propargylic pivaloates leading to fused bicyclic compounds.

gold - cyclization - pivaloate - catalyst - bicyclic compounds

References and Notes

For reviews, see:

1a Hashmi ASK. Hutchings GJ. Angew. Chem. Int. Ed.  2006,  45:  7896 

1b Gorin DJ. Toste FD. Nature (London)  2007,  446:  395 

1c Jiménez-Núñez E. Echavarren AM. Chem. Commun.  2007,  333 

2a Huang X. Zhang L. J. Am. Chem. Soc.  2007,  129:  6398 

2b Nieto-Oberhuber C. Pérez-Galán P. Herrero-Gómez E. Lauterbach T. Rodriguez C. López S. Bour C. Rosellon A. Cárdenas DJ. Echavarren AM. J. Am. Chem. Soc.  2008,  130:  269 

2c Luo T. Schreiber SL. Angew. Chem. Int. Ed.  2007,  46:  8250 

2d Johansson MJ. Gorin DJ. Staben ST. Toste FD. J. Am. Chem. Soc.  2005,  127:  18002 

2e Luzung MR. Markham JP. Toste FD. J. Am. Chem. Soc.  2004,  126:  10858 

2f Zhang L. Kozmin SA. J. Am. Chem. Soc.  2004,  126:  11806 

2g Zhang L. Kozmin SA. J. Am. Chem. Soc.  2005,  127:  6963 

2h C. Nieto-Oberhuber S. López AM. Echavarren AM. J. Am. Chem. Soc.  2005,  127:  6178 

2i Fürstner A. Hannen P. Chem. Commun.  2004,  2546 

3a Mézailles N. Ricard L. Gagosz F. Org. Lett.  2005,  7:  4133 

3b Nieto-Oberhuber C. Muñoz MP. López S. Jiménez-Núñez E. Nevado C. Herrero-Gómez E. Raducan M. Echavarren AM. Chem. Eur. J.  2006,  12:  1677 

4 Oh CH. Kim A. New J. Chem.  2007,  31:  1719 

For Au-catalyzed [2+2] cyclization, see:

5a Couty S. Meyer C. Cossy J. Angew. Chem. Int. Ed.  2006,  45:  6726 

5b Luzung MR. Mauleon P. Toste FD. J. Am. Chem. Soc.  2007,  129:  12402 

6

Typical Experimental Procedure for Cyclization of 4a to 7aIn a 5 mL new test tube were placed AuCl(PPh₃) (7.0 mg, 14.0 µmol, 5 mol%) and AgSbF₆ (4.8 mg, 14 µmol) and added dried DCE (1.0 mL) under argon atmosphere. After being stirred for 10 min at 0 °C, a DCE solution (0.5 mL) of diyne-propargylic pivaloate 4a (101.0 mg, 0.28 mmol) was added. The resulting mixture was stirred for 15 h at r.t. and the reaction was periodically monitored by TLC. Upon completion, the solvent was removed under vacuum and the crude product was subjected to flash column chroma-tography (SiO₂, n-hexane-EtOAc = 30:1) to afford the pure product 7a as a colorless oil. All new compounds were fully characterized by ¹H NMR, ¹³C NMR, IR, and HRMS (ESMS).
Compound 7a: IR (NaCl): 3301, 3064, 2940, 2869, 1707, 1671, 1491, 1287 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 8.07-8.04 (m, 2 H), 7.42-7.37 (m, 3 H), 3.47 (q, J = 4.0 Hz, 1 H), 3.40 (q, J = 4.0 Hz, 1 H), 2.68-2.49 (m, 2 H), 2.22 (td, J = 7.0, 3.2 Hz, 2 H), 1.95 (t, J = 2.4 Hz, 1 H), 1.83-1.68 (m, 5 H), 1.66-1.54 (m, 3 H), 1.49-1.38 (m, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 197.13, 155.44, 136.26, 132.49, 130.25, 128.93, 128.35, 84.19, 68.46, 43.75, 43.28, 40.06, 28.01, 26.31, 26.07, 23.16, 22.72, 18.35. HRMS: m/z calcd for C₂₀H₂₂ONa⁺: 301.3779; found: 301.3787.
Compound 7b: IR (NaCl): 3059, 3030, 2931, 2853, 2225, 1736, 1670, 1560, 1175 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 8.06-8.04 (m, 2 H), 7.39-7.37 (m, 5 H), 7.28-7.24 (m, 3 H), 3.45 (q, J = 3.6 Hz, 1 H), 3.39 (q, J = 3.6 Hz, 1 H), 2.71-2.52 (m, 2 H), 2.44 (t, J = 7.6 Hz, 2 H), 1.86-1.77 (m, 4 H), 1.73-1.54 (m, 6 H), 1.48-1.38 (m, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 197.23, 155.39, 136.35, 132.55, 131.55, 130.23, 128.94, 128.35, 128.14, 127.49, 123.97, 89.87, 80.89, 43.78, 43.33, 40.17, 28.33, 26.34, 26.09, 23.18, 22.97, 19.35. HRMS: m/z calcd for C₂₆H₂₆ONa⁺: 377.4733; found: 377.4778.
Compound 7c: IR (NaCl): 3065, 3030, 2945, 2857, 2247, 1797, 1634, 1490, 1228, 1172 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 7.88 (d, J = 3.8 Hz, 2 H), 7.57-7.54 (m, 2 H), 7.49 (t, J = 7.2 Hz, 1 H), 7.38 (t, J = 7.2 Hz, 2 H), 7.28-7.23 (m, 3 H), 3.64-3.56 (m, 2 H), 1.87-1.78 (m, 2 H), 1.74-1.63 (m, 2 H), 1.52-1.46 (m, 1 H), 1.42-1.32 (m, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 191.46, 153.85, 138.08, 136.24, 132.54, 132.40, 129.54, 128.94, 128.69, 128.39, 128.19, 45.69, 44.53, 26.49, 26.27, 23.29 29. HRMS: m/z calcd for C₂₀H₁₈ONa⁺: 297.3461; found: 297.3462.
Compound 7d: IR (NaCl): 3066, 2956, 2933, 2869, 2350, 1716, 1655, 1540, 1458 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 8.06-8.04 (m, 2 H), 7.40-7.37 (m, 3 H), 3.47-3.38 (m, 2 H), 2.64-2.46 (m, 2 H), 1.84-1.77 (m, 2 H), 1.74-1.56 (m, 5 H), 1.49-1.33 (m, 5 H), 0.92 (t, J = 7.2 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 197.87, 155.07, 136.52, 132.57, 130.15, 128.92, 128.32, 43.70, 43.34, 40.41, 26.32, 26.09, 25.80, 23.17, 22.43, 13.96. HRMS: m/z calcd for C₁₈H₂₂ONa⁺: 277.3559; found: 277.3554.
Compound 7e: IR (NaCl): 3058, 2942, 2859, 2252, 1747, 1636, 1578, 1445, 1334 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 7.96 (d, J = 8 Hz, 1 H), 7.74-7.69 (m, 2 H), 7.57 (d, J = 7.2 Hz, 2 H), 7.39-7.28 (m, 4 H), 6.93 (t, J = 7.6 Hz, 2 H), 3.86 (q, J = 3.6 Hz, 1 H), 3.68 (q, J = 3.6 Hz, 1 H), 2.31-2.27 (m, 1 H), 1.89-1.65 (m, 2 H), 1.86-1.77 (m, 2 H), 1.63-1.51 (m, 2 H), 1.44-1.34 (m, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 191.50, 154.83, 139.20, 137.60, 133.31, 131.96, 131.86, 130.83, 129.02, 128.95, 128.68, 128.20, 127.60, 127.01, 126.24, 125.79, 125.23, 124.89, 48.74, 45.71, 26.85, 25.58, 23.54. HRMS: m/z calcd for C₂₄H₂₀ONa⁺: 347.4042; found: 347.4042.
Compound 7f: IR (NaCl): 3056, 2956, 2930, 2858, 1655, 1506, 1460, 1391, 1198, 1026 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 7.97-7.84 (m, 3 H), 7.52-7.37 (m, 4 H), 3.62-3.50 (m, 2 H), 2.23-2.08 (m, 2 H), 2.04-2.01 (m, 1 H), 1.84-1.76 (m, 2 H), 1.61-1.58 (m, 2 H), 1.51-1.41 (m, 1 H), 1.38-1.26 (m, 4 H), 0.59 (t, J = 7.6 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 198.22, 155.35, 141.22, 133.55, 132.77, 130.74, 128.86, 128.51, 126.48, 126.20, 125.81, 125.41, 125.13, 48.87, 43.80, 39.96, 26.37, 26.23, 24.96, 23.47, 22.16, 13.52. HRMS: m/z calcd for C₂₂H₂₄ONa⁺: 327.4146; found: 327.4145.
Compound 7g: IR (NaCl): 3032, 2936, 2863, 2246, 1769, 1649, 1507, 1338 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 7.89-7.86 (m, 2 H), 7.54-7.47 (m, 3 H), 7.39-7.35 (m, 2 H), 7.26-7.24 (m, 1 H), 3.41-3.30 (m, 2 H), 2.06-1.96 (m, 1 H), 1.87-1.47 (m, 7 H). ¹³C NMR (100 MHz, CDCl₃): δ = 191.65, 157.03, 139.83, 138.07, 133.36, 132.40, 129.37, 128.86, 128.53, 128.41, 128.22, 39.68, 38.60, 24.10, 23.51, 18.82, 18.70. HRMS: m/z calcd for C₂₁H₂₀ONa⁺: 311.3721; found: 311.3725.
Compound 7h: IR (NaCl): 2961, 2860, 2255, 1794, 1714 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 8.01-7.98 (m, 2 H), 7.40-7.37 (m, 3 H), 3.19 (q, J = 6.0 Hz, 1 H), 3.13 (q, J = 5.6 Hz, 1 H), 2.62-2.43 (m, 2 H), 1.97-1.89 (m, 2 H), 1.78-1.68 (m, 2 H), 1.66-1.58 (m, 3 H), 1.57-1.42 (m, 4 H), 1.39-1.30 (m, 2 H), 1.27-1.22 (m, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 198.18, 158.27, 140.18, 133.32, 129.95, 128.78, 128.31, 40.80, 37.91, 37.56, 25.74, 23.94, 23.81, 22.43, 18.85, 18.70, 13.94. HRMS: m/z calcd for C₁₉H₂₄ONa⁺: 291.3824; found: 291.3830.
Compound 7i: IR (NaCl): 3051, 2905, 2322, 1745, 1678, 1487, 1145 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 8.04-8.02 (m, 2 H), 7.39-7.37 (m, 3 H), 3.46 (q, J = 3.6 Hz, 1 H), 3.41 (q, J = 3.6 Hz, 1 H), 2.69-2.64 (m, 1 H), 1.86-1.77 (m, 5 H), 1.74-1.68 (m, 2 H), 1.66-1.59 (m, 1 H), 1.50-1.41 (m, 3 H), 1.34-1.21 (m, 5 H). ¹³C NMR (100 MHz, CDCl₃): δ = 201.37, 155.99, 136.40, 132.64, 130.11, 128.85, 128.30, 47.53, 43.66, 43.56, 29.13, 28.13, 26.62, 26.19, 25.97, 25.87, 25.57, 23.18. HRMS: m/z calcd for C₂₀H₂₄ONa⁺: 303.3932; found: 303.3930.
Compound 7j: IR (NaCl): 3067, 3032, 2863, 2246, 1769, 1649, 1652, 1507, 1338 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 8.05-8.03 (m, 2 H), 7.43-7.41 (m, 3 H), 7.37-7.35 (m, 1 H), 7.23-7.15 (m, 2 H), 7.11-7.09 (m, 1 H), 4.21 (d, J = 4.8 Hz, 1 H), 3.79 (t, J = 4.8 Hz, 1 H), 2.61-2.49 (m, 2 H), 2.37-2.30 (m, 2 H), 1.65-1.50 (m, 2 H), 1.46-1.35 (m, 2 H), 1.30-1.21 (m, 2 H), 0.84 (t, J = 7.2 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 197.73, 155.56, 139.72, 137.17, 136.27, 132.32, 130.51, 130.02, 129.29, 129.00, 128.91, 128.80, 128.69, 128.60, 126.58, 126.39, 43.16, 41.42, 39.84, 26.48, 25.67, 39.84, 26.48, 25.67, 25.41, 22.53, 14.12. HRMS: m/z calcd for C₂₃H₂₄ONa⁺: 339.4253; found: 339.4254.
Compound 7k: IR (NaCl): 3065, 2949, 2845, 2358, 2249, 1728, 1634, 1598, 1579, 1501, 1446, 1289 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 8.05 (s, 4 H), 3.46 (q, J = 3.2 Hz, 2 H), 3.40 (q, J = 4 Hz, 2 H), 2.66-2.46 (m, 4 H), 1.80 (td, J = 13.6, 5.2 Hz, 4 H), 1.72-1.57 (m, 8 H), 1.47-1.30 (m, 8 H), 0.92 (t, J = 7.2 Hz). ¹³C NMR (100 MHz, CDCl₃): δ = 197.79, 154.25, 137.53, 133.82, 128.86, 43.68, 43.54, 40.47, 29.68, 26.35, 25.81, 23.16, 22.43, 13.98. HRMS: m/z calcd for C₃₀H₃₈O₂Na⁺: 453.6107; found: 453.6104.
Compound 7l: IR (NaCl): 2955, 2859, 2357, 1746, 1667, 1588, 1504, 1457, 1177 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 7.87 (d, J = 7.6 Hz, 4 H), 7.52-7.36 (m, 10 H), 3.62 (q, J = 3.2 Hz, 2 H), 3.54 (q, J = 3.6 Hz, 2 H), 1.82-1.62 (m, 8 H), 1.41-1.31 (m, 4 H). ¹³C NMR (100 MHz, CDCl₃): δ = 191.29, 137.31, 133.29, 128.90, 128.53, 128.47, 120.62, 45.92, 44.43, 26.48, 26.27, 23.27. HRMS: m/z calcd for C₃₄H₃₀O₂Na⁺: 493.5900; found: 493.5889.